Type IV phosphodiesterase inhibition improves cardiac contractility in endotoxemic rats

Neal J. Thomas, Joseph A. Carcillo, William A. Herzer, Zaichuan Mi, Stevan P. Tofovic, Edwin K. Jackson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Type IV phosphodiesterase inhibitors have a potential role in treating human sepsis. We examined the cardiac performance effects of type IV phosphodiesterase inhibition in vivo, in the absence and presence of catecholamines. Rats were randomized to receive either 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro 20-1724) at 0 (vehicle), 2 or 10 μg/kg/min. Utilizing a left ventricular catheter to measure cardiac performance, each animal received each of the two catecholamines, epinephrine and norepinephrine, in randomized order. Rats then received intravenous endotoxin and additional infusions of catecholamines. Ro 20-1724 at 2 μg/kg/min protected cardiac contractility during endotoxemia, and at 10 μg/kg/min increased cardiac contractility and protected cardiac function during endotoxemia. Neither dose interfered with the maximal contractile response to catecholamines. Type IV phosphodiesterase inhibition with Ro 20-1724 exerts beneficial effects on cardiac performance during septicemia in an in vivo animal model. Clinical studies of type IV phosphodiesterase inhibitors in critically ill patients are indicated.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1-2
StatePublished - Mar 28 2003

All Science Journal Classification (ASJC) codes

  • Pharmacology


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